The relative carcinogenicity of a number of cyclic N-nitrosamines can be related to the availability of a hydrogen alpha to the nitrosamine function and in a plane perpendicular to that containing the nitrosamine and its substituents. This proposal is designed to test this correlation by applying it to available published data and by designing and preparing N-nitrosamine structures which would be predicted to have enhanced carcinogenicity or lack of activity. Quantitative steady state kinetic parameters of microsomal nitrosamine metabolism will be determined and a quantitative estimation of the mutagenic potential of the metabolic products will be made using the Ames Assay. The relative carcinogenicity and organ specificity of these nitrosamines will be compared with these data. If the correlation of structure activity remains successful after these tests, an attempt will be made to rationalize the results in terms of the biochemical mechanism of carcinogenicity of N-nitrosamines.